dc.contributor.author | Rujas Díez, Edurne | |
dc.contributor.author | Kucharska, Iga | |
dc.contributor.author | Tan, Yong Zi | |
dc.contributor.author | Benlekbir, Samir | |
dc.contributor.author | Cui, Hong | |
dc.contributor.author | Zhao, Tiantian | |
dc.contributor.author | Wasney, Gregory A. | |
dc.contributor.author | Budylowski, Patrick | |
dc.contributor.author | Guvenc, Furkan | |
dc.contributor.author | Newton, Jocelyn C. | |
dc.contributor.author | Sicard, Taylor | |
dc.contributor.author | Semesi, Anthony | |
dc.contributor.author | Muthuraman, Krithika | |
dc.contributor.author | Nouanesengsy, Amy | |
dc.contributor.author | Burn Aschner, Clare | |
dc.contributor.author | Prieto, Katherine | |
dc.contributor.author | Bueler, Stephanie A. | |
dc.contributor.author | Youssef, Sawsan | |
dc.contributor.author | Liao-Chan, Sindy | |
dc.contributor.author | Glanville, Jacob | |
dc.contributor.author | Christie-Holmes, Natasha | |
dc.contributor.author | Mubareka, Samira | |
dc.contributor.author | Gray-Owen, Scott D. | |
dc.contributor.author | Rubinstein, John L. | |
dc.contributor.author | Treanor, Bebhinn | |
dc.contributor.author | Julien, Jean-Philippe | |
dc.date.accessioned | 2021-06-25T07:58:58Z | |
dc.date.available | 2021-06-25T07:58:58Z | |
dc.date.issued | 2021-06-16 | |
dc.identifier.citation | Nature Communications 12(1) : (2021) // Article ID 3661 | es_ES |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | http://hdl.handle.net/10810/52013 | |
dc.description.abstract | SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies
can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin
protomer as a modular subunit to drive oligomerization of antibody fragments and transform
antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform,
half-maximal inhibitory concentration (IC50) values as low as 9 × 10−14 M are achieved as a
result of up to 10,000-fold potency enhancements compared to corresponding IgGs. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain
on a single multivalent molecule conferred the ability to overcome viral sequence variability
together with outstanding potency and IgG-like bioavailability. The MULTi-specific, multiAffinity antiBODY (Multabody or MB) platform thus uniquely leverages binding avidity
together with multi-specificity to deliver ultrapotent and broad neutralizers against SARSCoV-2. The modularity of the platform also makes it relevant for rapid evaluation against
other infectious diseases of global health importance. Neutralizing antibodies are a promising
therapeutic for SARS-CoV-2. | es_ES |
dc.description.sponsorship | This work was supported by Natural Sciences and Engineering
Research Council of Canada discovery grant 6280100058 (J.-P.J.), by operating grant PJ4-169662 from the Canadian Institutes of Health Research (CIHR; B.T. and J.-P.J.), by
COVID-19 Research Fund C-094-2424972-JULIEN (J.-P.J.) from the Province of
Ontario Ministry of Colleges and Universities, by Bill and Melinda Gates Foundation
INV-023398 (J.-P.J.) and by the Hospital for Sick Children Foundation. This research
was also supported by the European Union’s Horizon 2020 research and innovation
program under Marie Sklodowska-Curie grant 790012 (E.R.), by a Hospital for Sick
Children Restracomp Postdoctoral Fellowship (I.K. and C.B.A.), by a CIHR Postdoctoral
Fellowship (Y.Z.T.), by a NSERC postgraduate doctoral scholarship (T.Z.), by a Vanier
Canada Graduate Scholarship (T.S.), by a CIHR Canada Graduate Scholarship— Master’s Award (A.N.), by the CIFAR Azrieli Global Scholar program (J.-P.J.), by the Ontario
Early Researcher Awards program (J.-P.J.), and by the Canada Research Chairs program
(J.L.R., B.T., and J.-P.J.). Cryo-EM data were collected at the Toronto High Resolution
High Throughput cryo-EM facility, biophysical data at the Structural & Biophysical Core
facility, and biodistribution data at the CFI 3D Facility at University of Toronto, all
supported by the Canada Foundation for Innovation and Ontario Research Fund. X-ray
diffraction experiments were performed at GM/CA@APS, which has been funded in
whole or in part with federal funds from the National Cancer Institute (ACB-12002) and
the National Institute of General Medical Sciences (AGM-12006). The Eiger 16 M
detector at GM/CA-XSD was funded by NIH grant S10 OD012289. This research used
resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of
Science user facility operated for the DOE Office of Science by Argonne National
Laboratory under contract DE-AC02-06CH11357 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/790012 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | pandemics | es_ES |
dc.subject | modularity | es_ES |
dc.subject | antibodies | es_ES |
dc.subject | public health | es_ES |
dc.subject | severe acute respiratory syndrome coronavirus 2 | es_ES |
dc.subject | infectious diseases | es_ES |
dc.subject | Covid-19 | es_ES |
dc.subject | viral diseases | es_ES |
dc.subject | domains | es_ES |
dc.subject | oligomerization | es_ES |
dc.subject | bioavailability | es_ES |
dc.subject | viruses | es_ES |
dc.subject | neutralizers | es_ES |
dc.subject | neutralization | es_ES |
dc.subject | apoferritin | es_ES |
dc.subject | severe acute respiratory syndrome | es_ES |
dc.subject | immunoglobulin G | es_ES |
dc.subject | viral infections | es_ES |
dc.subject | avidity | es_ES |
dc.title | Multivalency Transforms SARS-CoV-2 Antibodies Into Ultrapotent Neutralizers | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www-proquest-com.ehu.idm.oclc.org/docview/2541557730/abstract/BB99936C49A140DCPQ/1?accountid=17248 | es_ES |
dc.identifier.doi | 10.1038/s41467-021-23825-2 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |